GASTROINTESTINAL TRACT

INFECTION
SY. MIFTAHUL EL JANNAH
Flora normal
Enterobacteriaceae, kecuali Salmonella, Shigella,
Yersinia, Vibrio dan Campylobacter
Non dextrose fermenting Gram negative rods
Enterococci
Alpha hemolytic dan non hemolytic Streptococci
Diphtheroids
Sedikit S. aureus
Sedikit Yeast
Banyak anaerob
Saat lahir usus steril, mo masuk bersama makanan, tdd Streptococcus asam
laktat dan Lactobacillus .
For an infection to occur, the pathogen must be ingested in sufficient numbers or
possess attributes to elude the host defenses of the upper gastrointestinal tract and
reach the intestine
Perkembangan pola makan merubah flora normal usus
Asam lambung menjaga jumlah mo seminimal mungkin [10
3
-10
5
/g isi lambung]
Seiring pH usus menjadi basa flora normal meningkat.
Duodenum orang dewasa 10
8
-10
10
bakteri/g isi usus
Jejunum dan ileum 10
5
-10
8
bakteri/g
Caecum dan kolon transversum 10
3
-10
5
bakteri/g
Kolon sigmoid dan rektum 10
11
bakteri/g
Every day we swallow
large numbers of
microorganisms.
Because of the body's
defense mechanisms,
however, they rarely
succeed in surviving
the passage to the
intestine in sufficient
numbers to cause
infection.
Peran
Sintesis vitamin K
Konversi pigmen pigmen empedu dan asam
asam empedu
Penyerapan zat-zat makanan dan hasil
pemecahannya
Perlawanan terhadap mo patogen
Figure 22.1 As well as many colloquial expressions, several different clinical terms
are used to describe infections of the gastrointestinal tract. Diarrhea without
blood and pus is usually the result of enterotoxin production, whereas the
presence of blood and/or pus cells in the feces indicates an invasive infection with
mucosal destruction.
A wide range of microbial
pathogens is capable of
infecting the gastrointestinal
tract, and the important
bacterial and viral pathogens
They are acquired by the
fecal-oral route, from fecally
contaminated food, fluids or
fingers Many different
pathogens cause infections
of the gastrointestinal tract.
Some are found in both
humans and animals while
others are strictly human
parasites.
Infections of the
gastrointestinal tract can be
grouped into those that
remain localized in the gut and
those that invade beyond the
gut to cause infection in other
sites in the body. In order to
spread to a new host,
pathogens are excreted in
large numbers in the feces and
must survive in the
environment for long enough
to infect another person
directly or indirectly through
contaminated food or fluids.
The damaging effects resulting from infection of the
gastrointestinal tract
Escherichia coli is a major cause of gastrointestinal infection, particularly in developing
countries and in travelers. There is a range of pathogenic mechanisms within the species,
resulting in more or less invasive disease. *Specialized tests are given in italics. (LT, heat-
labile enterotoxin; ST, heat-stable enterotoxin.)
Bacterial causes of diarrhea
Escherichia coli
This is one of the most versatile of all bacterial pathogens.
Some strains are important members of the normal gut flora in
man and animals, whereas others possess virulence factors that
enable them to cause infections in the intestinal tract or at
other sites, particularly the urinary tract
Strains that cause diarrheal disease do so by several distinct
pathogenic mechanisms and differ in their epidemiology
There are six distinct groups of E. coli with different pathogenetic mechanisms Initially
all diarrhea-associated Escherichia coli were termed enteropathogenic E. coli
(EPEC).
Enteropathogenic E. coli (EPEC),
enterotoxigenic E. coli (ETEC),
enterohemorrhagic E. coli (EHEC) more important in developed
enteroinvasive E. coli (EIEC),
enteroaggregative E. coli (EAEC),
and diffuse-aggregative E. coli (DAEC).
The diarrhea produced by E. coli varies from mild to severe, depending upon the strain
and the underlying health of the host.
EIEC and EHEC strains both cause bloody diarrhea
EPEC and ETEC are the most
important contributors to global
incidence of diarrhea
Enteropathogenic E. coli (EPEC)
Do not appear to make any toxins.
They do produce bundle-forming pili (Bfp), intimin (an
adhesin) and an associated protein (translocated intimin
receptor, Tir). These virulence factors allow bacterial
attachment to epithelial cells of the small intestine, leading
to disruption of the microvillus (an 'attaching-effacing'
mechanism of action) leading to diarrhea.

Electron micrograph of enteropathogenic Escherichia coli adhering to
the brush border of intestinal mucosal cells with localized destruction
of microvilli. (Courtesy of S Knutton.)
The clinical
features of
bacterial
diarrhea
infection. It
is difficult, if
not
impossible,
to
determine
the likely
cause of a
diarrheal
illness on
the basis of
clinical
features
alone, and
laboratory
investigatio
ns are
essential to
identify the
pathogen.
Enterotoxigenic E. coli (ETEC)
possess colonization factors (fimbrial
adhesins.
ETEC diarrhea in children in developing
countries may be clinically indistinguishable
from cholera

These bind the bacteria to specific receptors on the cell membrane of the
small intestine. These organisms produce powerful plasmid-associated
enterotoxins which are characterized as being either heat labile (LT) or heat
stable (ST):
Heat-labile enterotoxin LT-I is very similar in structure and mode of action to
cholera toxin produced by V. cholerae, and infections with strains producing LT-I
can mimic cholera, particularly in young and malnourished children.
Heat-stable enterotoxins (STs) in addition to or instead of LT. STs have a similar
but distinct mode of action to that of LT. ST
A
activates guanylate cyclase activity,
causing an increase in cyclic guanosine monophosphate, which results in
increased fluid secretion. Immunoassays are commercially available for the
identification of ETEC.
Electron micrograph of enterotoxin Escherichia coli, showing pili necessary
for adherence to mucosal epithelial cells. (Courtesy of S Knutton.)
Enterohemorrhagic E. coli (EHEC)
Isolates produce a verotoxin
The verotoxin (i.e. toxic to tissue cultures of 'vero'cells) is essentially identical to Shiga (Shigella)
toxin. After attachment to the mucosa of the large intestine (by the 'attaching-effacing'
mechanism also seen in EPEC) the produced toxin has a direct effect on intestinal epithelium,
resulting in diarrhea
EHEC cause hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). In HC there is
destruction of the mucosa and consequent hemorrhage; this may be followed by HUS.
Verotoxin receptors have been identified on renal epithelium and may account for the kidney
involvement. While there are many serotypes of EHEC, the most common one in the USA is
O157:H7.
HUS is characterized by acute renal failure, anemia and thrombocytopenia, and there may be
neurologic complications HUS is the most common cause of acute renal failure in children in
the UK and USA.
Verotoxin-producing Escherichia coli infection, showing fibrin
'thrombi' in glomerular capillaries in hemolytic-uremic syndrome.
(Weigert stain.) (Courtesy of HR Powell.)
Enteroinvasive E. coli (EIEC)
Attach specifically to the mucosa of the large intestine
Utilizing plasmid-associated genes, they invade the cells by endocytosis.
Inside the cell they lyse the endocytic vacuole, multiply and spread to
adjacent cells, causing tissue destruction, inflammation, necrosis and
ulceration, resulting in blood and mucus in stools
Enteroaggregative E. coli (EAEC)
Derive their name from their characteristic attachment pattern to tissue culture
cells .
The pattern is an aggregative or 'stacked brick' formation. These organisms act in
the small intestine to cause persistent diarrhea especially in children in developing
countries.
Their aggregative adherence ability is due to plasmid-associated fimbriae.
EAEC also produce heat-labile toxins (an enterotoxin and a toxin related to E. coli
hemolysin) but their role in diarrheal disease is uncertain.
Diffuse-aggregative E. coli (DAEC)
Produce an alpha hemolysin and cytotoxic necrotizing factor 1
They are also known as diffuse-adherent or cell-detaching E. coli.
Their role in diarrheal disease, especially in young children, is incompletely
understood and somewhat controversial, with some studies reporting no
association.



Specific tests are needed to identify strains of pathogenic E. coli :
Because E. coli is a member of the normal gastrointestinal flora, specific tests are
required to identify strains that may be responsible for diarrheal disease.
Infections are more common in children and are also often travel-associated, and these
factors should be considered when samples are received in the laboratory.
It is important to note that specialized tests beyond routine stool cultures are required
to identify specific diarrhea-associated E. coli types. Such tests are not ordinarily
performed with uncomplicated diarrhea, which is usually self-limiting.
Antibacterial therapy is not indicated for E. coli diarrhea
Fluid replacement may be necessary, especially in young children. Treatment of HUS is
urgent and may involve dialysis.
Provision of a clean water supply and adequate systems for sewage disposal are
fundamental to the prevention of diarrheal disease.
Food and unpasteurized milk can be important vehicles of infection, especially for EIEC
and EHEC, but there is no evidence of an animal or environmental reservoir.

Salmonella
Salmonellae common cause of food-associated diarrhea in many developed
countries, in some countries (e.g. the USA and UK) they have been relegated to second
place by Campylobacter.
The most important of which, for human infection, is Salmonella enterica.
All salmonellae except for Salmonella typhi and S. paratyphi are found in animals as well
as humans. There is a large animal reservoir of infection, which is transmitted to man via
contaminated food, especially poultry and dairy products.
Waterborne infection is less frequent.
Salmonella infection is also transmitted from person to person, and secondary spread
can therefore occur, for example within a family after one member has become infected
after consuming contaminated food
Salmonellae are almost always acquired orally in food or drink that is contaminated
The recycling of salmonellae. With the exception of Salmonella typhi,
salmonellae are widely distributed in animals, providing a constant source of
infection for man. Excretion of large numbers of salmonellae from infected
individuals and carriers allows the organisms to be 'recycled'
MO lolos dari lambung multiplikasi dlm sal. Cerna menembus mukosa usus
di fagosit oleh makrofag
keluar dari SDP menyebar, multiplikasi
duktus toraksikus
aliran darah [bakteriaemia fase
pertama/primer] pd hari ke-7
10
menginfeksi hepar, kandung empedu,
limfe, ginjal dan sumsum tulang
multiplikasi dalam RES
aliran darah [jumlah semakin banyak,
bakteriaemia fase kedua/sekunder],
melepaskan endotoksin
[demam tinggi & gejala tifoid lainnya]
Bakteri dari kandung empedu
usus halus & jaringan limfoid
perdarahan
perforasi usus
The passage of salmonellae through
the body. The vast majority of
salmonellae cause infection
localized to the gastrointestinal tract
and do not invade beyond the gut
mucosa. (cAMP, cyclic adenosine
monophosphate.)
Salmonella diarrhea can be diagnosed by culture on selective media
The organisms are not fastidious and can usually be isolated within 24 hours, although
small numbers may require enrichment in selenite broth before culture. Preliminary
identification can be made rapidly, but the complete result, including serotype, takes at
least 48 hours
Fluid and electrolyte replacement may be needed for salmonella diarrhea
Diarrhea is usually self-limiting and resolves without treatment. Unless there is
evidence of invasion and septicemia, antibiotics should be positively discouraged
because they do not reduce the symptoms or shorten the illness, and may prolong
excretion of salmonellae in the feces
Salmonellae may be excreted in the feces for several weeks after a salmonella infection
Pengendalian
The large animal reservoir makes it impossible to eliminate the organisms, and
preventive measures must therefore be aimed at 'breaking the chain' between animal
and man, and from person to person.
Such measures include: maintaining adequate standards of public health (clean drinking
water and proper sewage disposal);
Education programs on hygienic food preparation.
Following an episode of salmonella diarrhea, an individual can continue to carry and
excrete organisms in the feces for several weeks. Although in the absence of symptoms
the organisms will not be dispersed so liberally into the environment, thorough
handwashing before food handling is essential.
People employed as food handlers are excluded from work until three specimens of
feces have failed to grow salmonella.

Campylobacter
Campylobacters are among the commonest causes of diarrhea
Campylobacter spp. are curved or S-shaped Gram-negative rods
They have long been known to cause diarrheal disease in animals, but are also
one of the most common causes of diarrhea in humans.
The enterobacteria as they are microaerophilic and thermophilic (growing well
at 42C); they do not therefore grow on the media used for isolating E. coli and
salmonellae.
Several species of the genus Campylobacter are associated with human disease,
but Campylobacter jejuni is by far the most common. Helicobacter pylori,
previously classified as Campylobacter pylori, is an important cause of gastritis
and gastric ulcers
Campylobacter jejuni infection. Gram stain showing
Gram-negative, S-shaped bacilli. (Courtesy of I Farrell.)
As with salmonellae, there is a large animal reservoir of campylobacter in cattle,
sheep, rodents, poultry and wild birds.
Infections are acquired by consumption of contaminated food, especially poultry,
milk or water. Household pets such as dogs and cats can become infected and
provide a source for human infection, particularly for young children.
Person to person spread by the fecal-oral route is rare, as is transmission from food
handlers.
Campylobacter diarrhea is clinically similar to that caused by other bacteria such as
salmonella and shigella
Pathology and histologic appearances of ulceration and inflamed bleeding mucosal
surfaces in the jejunum, ileum and colon are compatible with invasion of the bacteria
but the production of cytotoxins by C. jejuni has also been demonstrated. Invasion
and bacteremia are not uncommon, particularly in neonates and debilitated adults.
Inflammatory enteritis caused by
Campylobacter jejuni, involving the entire
mucosa, with flattened atrophic villi, necrotic
debris in the crypts and thickening of the
basement membrane. (Cresyl-fast violet stain.)
(Courtesy of J Newman.)
The clinical presentation is similar to that of diarrhea
caused by salmonellae and shigella, although the disease
may have a longer incubation period and a longer duration.
Erythromycin is used for severe campylobacter diarrhea.
Erythromycin is the antibiotic of choice for cases of
diarrheal disease that are severe enough to warrant
treatment.
Invasive infections may require treatment with an
additional antibiotic (e.g. quinolone, aminoglycoside, etc.).

Cholera
Cholera is an acute infection of the gastrointestinal tract
Caused by the comma-shaped Gram-negative bacterium V.
cholerae. V. cholerae is a free-living inhabitant of fresh water, but
causes infection only in humans
Cholera flourishes in communities with inadequate clean drinking
water and sewage disposal
The 1990s have witnessed the seventh pandemic of cholera
spreading into Latin America. The disease remains endemic in
southeast Asia and parts of Africa and South America.
Scanning electron micrograph of Vibrio cholerae showing comma-
shaped rods with a single polar flagellum. 13000. (Courtesy of DK
Banerjee.)
Asymptomatic human carriers are believed to be a
major reservoir.
The disease is spread via contaminated food; shellfish
grown in fresh and estuarine waters have also been
implicated. Direct person to person spread is thought to
be uncommon.
V. cholerae serotypes are based on somatic (O) antigens
Serotype O1 is the most important and is further
divided into two biotypes: classical and El Tor.
Vibrio cholerae serotype O1, the cause of cholera, can be subdivided into different
biotypes with different epidemiologic features, and into serosubgroups and phage types
for the purposes of investigating outbreaks of infection. Although V. cholerae is the most
important pathogen of the genus, other species can also cause infections of both the
gastrointestinal tract and other sites.
The severe watery non-bloody diarrhea is known as rice water stool
because of its appearance and can result in the loss of one liter of
fluid every hour.
It is this fluid loss and the consequent electrolyte imbalance that
results in marked dehydration, metabolic acidosis (loss of
bicarbonate), hypokalemia (potassium loss) and hypovolemic shock
resulting in cardiac failure.
Untreated, the mortality from cholera is 40-60%; rapidly instituted
fluid and electrolyte replacement reduces the mortality to less than
1%.
sekresi cairan isotonus dari dinding usus.
MO lolos dari barrier asam lambung
usus halus, bermultiplikasi dan membentuk
eksotoksin disebut enterotoksin
bereaksi dengan reseptor pada
membran sel epitel usus
mengaktifkan adenilat siklase, mengakibatkan
Meningkatnya siklik adenosin monofosfat/cAMP
merangsang perubahan ATP menjadi ADP
ADP merangsang pengeluaran air dan elektrolit
oleh dinding usus ke dalam rongga usus dan
menahan penyerapan Na+ oleh dinding usus
The production of an
enterotoxin is central to
the pathogenesis of
cholera, but the
organisms must possess
other virulence factors to
allow them to reach the
small intestine and to
adhere to the mucosal
cells.
Rice water stool in cholera.
(Courtesy of AM Geddes.
SHIGELLA sp
Infeksi peroral, terutama melalui makanan jenis
sayuran, susu dan protein tinggi
Dosis infeksi 10
3
kuman
Berat ringannya tergantung spesies yang
meninfeksi paling berat S. dysentriae,
kemudian berturut-turut S. flexneri, S. boydii dan
yang paling ringan S. sonnei.
MO melewati lambung
usus halus
kolon, ditangkap oleh epitel
multiplikasi, menyebabkan rusaknya sel epitel
menginfeksi jaringan sekitar
reaksi radang
nekrotik, pengelupasan epitel,
perdarahan. [tidak pernah terjadi
perforasi dan masuk ke organ dalam]
Shigella spp
Bentuk sel bakteri
Koloni bakteri pada agar SSA
Shigellosis. Histology of the colon showing disrupted epithelium covered by
pseudomembrane and interstitial infiltration. Mucin glands have discharged their
contents and the goblet cells are empty. (Colloidal iron stain.) (E, epithelium; I,
interstitial infiltration; M, mucin in glands; P, pseudomembrane.) (Courtesy of RH
Gilman.)
Yersinia enterocolitica
member of the Enterobacteriaceae and is a cause of food-associated infection
especially among infants and particularly in colder parts of the world
Y. enterocolitica is found in a variety of animal hosts including rodents, rabbits,
pigs, sheep, cattle, horses and domestic pets. Transmission to humans from
household dogs has been reported. The organism survives and multiplies, albeit
more slowly, at refrigeration temperatures (4C) and has been implicated in
outbreaks of infection associated with contaminated milk as well as other foods.
The mechanism of pathogenesis is unknown, but the clinical features of the
disease result from invasion of the terminal ileum, necrosis in Peyer's patches and
an associated inflammation of the mesenteric lymph nodes
Yersinia enterocolitica infection of the ileum,
showing superficial necrosis of the mucosa and
ulceration. (Courtesy of J Newman.)
CLOSTRIDIUM PERFRINGENS
Merupakan bakteri Gram positip yang membentuk endospora, anerob
obligat, menghasilkan enterotoksin yang tidak dihasilkan pada makanan
sebelum dikonsumsi, tetapi dihasilkan bila bakteri berkolonisasi di usus.
Bakteri terdapat di tanah, usus manusia dan hewan, daging mentah,
unggas dan bahan pangan kering.
Gejala timbul 8-24 jam setelah mengkonsumsi pangan yang tercemar
bentuk vegetatip bakteri dalam jumlah besar, berupa sakit perut, mual
dan diare jarang disertai muntah. Gejala dapat berlanjut selama 1-2
minggu [terutama pada anak-anak dan manula].
Self limited

CLOSTRIDIUM PERFRINGENS
Jenis makanan yang mudah terkontaminasi: saus
daging yang disimpan pada suhu yang menunjang
perkecambahan spora [30-37
0
C]
Belum ada pengobatan khusus
Pencegahan: Tidak menyimpan makanan yang sudah
matang pada suhu kamar untuk jangka waktu yang
lama.


Gram stain of Clostridium perfringens.
Downloaded from: StudentConsult (on 20 October 2009 07:04 AM)
2005 Elsevier
GAMBAR 2. Growth of Clostridium perfringens on sheep blood agar. Note the flat,
spreading colonies and the hemolytic activity of the organism. A presumptive identification
of C. perfringens can be made by detection of a zone of complete hemolysis (caused by the
;-toxin) and a wider zone of partial hemolysis (caused by the ;-toxin), combined with the
characteristic microscopic morphology.
Downloaded from: StudentConsult (on 20 October 2009 07:04 AM)
2005 Elsevier
Distribution of Lethal Toxins in Clostridium perfringens Types A to E
Type Lethal Toxins
Alpha Beta
Epsilon Iota
A + -
- -
B + +
+ -
C + +
- -
D + -
+ -
E + -
- +
Clostridium perfringens is linked
with two forms of food-associated
infection. The common,
enterotoxin-mediated infection
(left) is usually acquired by eating
meat or poultry that has been
cooked enough to kill vegetative
cells, but not spores. As the food
cools, the spores germinate. If
reheating before consumption is
inadequate (as it often is in mass
catering outlets), large numbers of
organisms are ingested. The rare
form associated with -toxin-
producing strains (right) causes a
severe necrotizing disease.
Bacillus cereus
Bakteri berbentuk batang. Gram
positip, aerob,membentuk
endospora yang tahan panas dan
radiasi
Keracunan
menelan bakteri atau bentuk
sporanya bakteri bereproduksi
dan menghasilkan toksin di dalam
usus
mengkonsumsi pangan yang telah
mengandung toksin

Bacillus cereus
Sel B. cereus dengan
mikroskop elektron
Koloni di media agar darah
MIFTAHEL-2006
Bacillus cereus
Terdapat dua tope toksin: menyebabkan diare dan
muntah/emesis
Toksin penyebab diare, maka
gejala yang timbul berhubungan
dengan saluran bagian bawah,
berupa mual, nyeri perut seperti
kram, diare berair. Terjadi 8-16
jam setelah mengkonsumsi
pangan. Bakteri penghasil toksin
penyebab diare ini umumnya
mencemari sayuran dan daging.
Toksin penyebab muntah, gejala
yang timbul akan lebih bersifat
lebih parah dan akut dan
berhubungan dengan saluran
pencernaan bagian atas berupa
mual dan muntah yang dimulai
setelah 1-6 jam setelah
mengkonsumsi pangan yang
tercemar. Bakteri pengahasil
toksin ini mudah mencemari
pangan yang banyak
mengandung pati /nasi yang
didinginkan secara lambat dan
disimpan pada suhu kamar dan
tunas sayuran


Bacillus cereus
Pencegahan:
Pengendalian suhu yang efektif untuk mencegah
pertunasan dan pertumbuhan spora
mengolah makanan dengan pemanasan bertekanan,
menggoreng, tidak menyimpan nasi pada suhu ruang

Bacillus cereus can cause two
different forms of food-
associated infection. Both
involve toxins
Rotaviruses
These are morphologically characteristic viruses with a genome
consisting of 11 separate segments of double-stranded RNA.
Different rotaviruses infect the young of many mammals,
including children, kittens, puppies, calves, foals and piglets, but
it is thought that viruses from one host species occasionally
cross-infect another.
There are at least two human serotypes. Replicating rotavirus
causes diarrhea by damaging transport mechanisms in the gut
Viral diarrhea
Rotavirus. The virus particles (65 nm in diameter) have a well-
defined outer margin and capsules radiating from an inner core
to give the particle a wheel-like (hence 'rota') appearance.
(Courtesy of JE Banatvala.)
Replicating rotavirus causes diarrhea by damaging transport mechanisms in the
gut. The replicating virus damages transport mechanisms in the gut, and loss of
water, salt and glucose causes diarrhea
The incubation period is 1 to 2 days. After virus replication in intestinal epithelial
cells there is an acute onset of vomiting, which is sometimes projectile, and
diarrhea which lasts from 4 to 7 days
Infected cells in the intestine are destroyed, resulting in villous atrophy. The villi,
long finger- like projections, become flattened resulting in the loss of both the
surface area for absorption and the digestive enzymes, and raised osmotic
pressure in the gut lumen causes diarrhea.

The mechanism of rotavirus
diarrhea. Other viruses may
have different mechanisms.
VIRUS POLIO
Didapat pada susu yang tidak dipasteurisasi
Menimbulkan penyakit poliomielitis
Virus masuk bersama susu multiplikasi di tonsil dan
kelenjar orofaring aliran limfe/limfogen menyebar
ke bercak peyer dalam dinding usus SSP serabut
motorik ke sumsum tulang belakang atau otak
Virus dapat ditemukan dalam tonsil dan tinja

Virus polio
Morfologi sel
Struktur sel
VIRUS HEPATITIS A
Jenis makanan: susu, sayuran , daging dan
kerang-kerangan dalam keadaan kurang
masak
Sumber kontaminan: air, feses, penjamah
makanan yang carier virus hepatitis A


Virus Hepatitis
Bentuk sel
Struktur sel
FOOD POISONING
'food poisoning' is restricted to the diseases caused by
toxins elaborated by contaminating bacteria in food
before it is consumed
B. cereus
Staph. aureus enterotoxin Eight different enterotoxins
are produced by different strains of Staph. aureus
Cl. botulinum toxin
Staphylococcus aureus produces at least eight immunogically
distinct enterotoxins, the most important of which are listed
here. Strains may produce one or more of the toxins
simultaneously. Enterotoxin A is by far the most common in
food-associated disease.